Cross-linked polyimine and use thereof for the immobilization of acidic or electrophilic compounds present in a solution

ABSTRACT

The invention relates to a process for immobilizing acidic or electrophilic compounds in a solution. The process is characterized in that it consists in bringing a crosslinked polyimine, which is insoluble in the medium and in which the imino groups are —NH-groups, into contact with said compounds and in then separating, by filtration, the modified polyimine obtained. The crosslinked polyimine comprises linear segments composed of —HN—R 1 —NH—R 2 —Ar—R 3 -units in which R 1 , R 2  and R 3  are identical or different alkylene or alkenylene groups and Ar represents an aromatic group. The process is of use for fixing undesirable compounds or for purifying acidic compounds.

BACKGROUND OF THE INVENTION

1. Field of the invention:

The invention relates to a polymer material which can be used fortrapping byproducts and excess reactants in a reaction medium.

2. Brief Description of the Related Art

During the performance of a chemical reaction in order to prepare adesired product, undesirable byproducts are often obtained and have tobe removed. In addition, the reaction medium may comprise excessreactants which also have to be removed. The use has been envisaged ofpolymers on which the undesirable compounds may become fixed.

The proposal has been made to use polyimines immobilized on a supportfor removing acidic compounds in an organic solvent. For example, DE 10143 171 discloses a process for the preparation of a material for theremoval of acids from an aprotic organic liquid, said material beingcomposed of a polyalkyleneimine fixed to a support, for example silica.Yoshida Hiroyuki (Ind. Eng. Chem. Res.; vol. 33, No. 4, April 1994, pp.854-859) describes the adsorption of a strong acid on a weakly basicexchanger composed of a polyethyleneimine fixed to a highly porouschitosan. JP 62216641 discloses a polyethyleneimine having a molecularweight of greater than 5000 adsorbed on a support (for example, a porousresin) and its use as adsorbent for strong acids, surfactants or heavymetals. The polyimine is adsorbed on the porous resin by immersion ofthe resin in a polyimine solution. It is thus a polyimine soluble inorganic solvents which is immobilized on a support. The document U.S.Pat. No.5,162,404 discloses a sponge composed of cellulose and an“immobilized” polyethyleneimine fixed to the cellulose. Thepolyethyleneimine is a water-soluble branched polymer which comprisesprimary, secondary or tertiary amine groups separated by —CH₂CH₂- groupsand which is rendered insoluble by crosslinking using a halogenated ornonhalogenated carboxylic acid or a polyhalogenated aliphatic compoundof low molecular weight which reacts with the N atoms of the aminegroups. In all these processes, however, there are a number ofdisadvantages to the immobilization of the polyimine on a support.First, the preparation of the immobilization support requires two stages(preparation of the polyimine and then fixing of the polyimine on thesupport), which increases the production costs. Secondly, for a givenamount of support, the number of working functional groups is markedlylower when the polyimine is fixed to a support.

The proposal has been made to use an insoluble polymer as immobilizationagent for a compound in solution. The polymers conventionally used arepoly(styrene-divinyl-benzene)s carrying reactive functional groups whichmake possible the fixing of the compounds to be removed (cf. WO97/42230and J. Chem. Soc., Perkin Trans. 1, 2000, p. 4133-4195). However, thepolymers of this type cannot be used in aqueous media or in methanol. Inaddition, they have a relatively low level of active functional groups,which limits their performance.

SUMMARY OF THE INVENTION

The aim of the present invention is to provide a process for efficientlyremoving, using an insoluble immobilization agent, undesirable acidic orelectrophilic compounds in water and the organic solvents generally usedfor the synthesis of organic compounds.

A subject matter of the invention is a process for immobilizing acidicor electrophilic compounds present in a solvent. It is characterized inthat it consists in bringing a crosslinked polyimine, in which the iminogroups are —NH—groups, into contact with said compounds, saidcrosslinked polyimine being insoluble in said solvent, and inseparating, by filtration, the modified polyimine obtained.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The contacting operation can advantageously be carried out at ambienttemperature. The duration of the contact varies according to the natureof the compounds. Generally, a duration of between 1 hour andapproximately 10 hours is sufficient.

A crosslinked polyimine which is particularly appropriate for theimplementation of the process of the invention comprises linear segmentscomposed of —HN—R¹—NH—R²—Ar—R³- units in which R¹, R² and R³ areidentical or different alkylene or alkenylene groups and Ar representsan aromatic group.

R¹, R² and R³ are preferably alkylene or alkenylene groups having from 1to 10 carbon atoms. The aromatic group Ar is preferably a φ or φ-φ groupin which φ represents a phenyl optionally carrying one or moresubstituents. The substituents of the phenyl group can be chosen fromalkyl, aryl, alkyloxy, alkoxycarbonyl, halogen or NO₂ groups.

The presence of phenyl groups in the repeat units confers amphiphilicproperties on the polyimine which allow it to be used both inhydrophobic media and in hydrophilic media.

In a polyimine used for the process of the present invention, thecrosslinking nodes can be, for example, of theC(R⁴NH—R²—Ar—R³—)_(4−n)(R⁴NH₂)_(n) or N(R⁴NH—R^(2 —Ar—R) ₃—)₃ type inwhich R⁴ represents an alkylene group preferably having from 1 to 10carbon atoms and n is 0 or 1.

A polyimine as defined above has a very high content of NH groups. Forexample, it is of the order of 11 mmol/g when R¹ and R⁴ are —CH₂CH₂—andR² and R³ are —CH₂—. In addition, although insoluble in water and in theorganic solvents normally used for various chemical reactions, it swellswhen it is placed in such solvents, that is to say that it has anability to accept solvent and reactant molecules within the molecularmesh. The active NH sites of the polyimine are thus accessible and canreact with various compounds, in particular with inorganic or organicacids and with electrophilic compounds. This property is taken advantageof in trapping compounds of this nature which are present in a reactionmedium and which are undesirable. The high content of NH groups isconfirmed by the IR spectrum of the polyimine, which exhibits a verybroad band at approximately 3300-3400 cm⁻¹, characteristic of the NHgroups.

The crosslinked polyimines which can be used in the process of theinvention can be prepared by a single-stage process which consists inpolycondensing a diamine H₂N—R¹—NH₂ with a dihalide X—R²—Ar—R³—X in anorganic solvent in the presence of a crosslinking agent and of an agentcapable of trapping the hydrohalic acid formed. R¹, R², R³ and Ar are asdefined above.

It is preferable to use a diamine and a crosslinking agent which have anequivalent reactivity with respect to the dihalide in order to obtain arandom distribution of the crosslinking nodes. For this purpose, it isadvantageous to choose a tetramine N(R⁴NH₂)₃ or C(R⁴NH₂)₄. Thecrosslinking agent/diamine molar ratio is preferably less than or equalto 4 mol %. Under these conditions, the polymer obtained remainscompletely insoluble in the solvents (water or organic solvents) but itswells well in said solvents (with the exception of alkanes).

Preference is given, among dihalides, to dichlorides.

The organic solvent used for preparing a polyimine is preferably chosenfrom those which make it possible to dissolve the monomers and to causethe growing polymer to swell. Mention may be made, by way of examples,of toluene and DMF.

Mention may be made, as agent capable of trapping the hydrohalic acid,of tertiary amines, for example triethylamine or diisopropylethylamine.

The process of the invention can be employed for the trapping andremoval of inorganic acids, of organic acids or of various electrophiliccompounds which are formed as byproducts during a reaction or which arereactants used in excess in a reaction mixture.

The trapping of an inorganic acid HX (X is, for example, Cl, HSO₄, NO₃,H₂PO₄, Br or I) or an organic acid HX (X is, for example, a carboxylateor a sulfonate) is carried out according to the following reactionscheme, in which the compound 4 represents a crosslinked polyimineaccording to the invention:

As the polyimine is amphiphilic, it can be used to trap inorganic acidsin the aqueous phase as in the organic phase. Thus, the reaction mediumcomprising the desired product is neutralized and freed fromneutralization salts by simple filtration. This facilitates is theisolation of the desired product insofar as stages of extraction atdifferent pH values are avoided.

The trapping of an electrophilic compound is carried out according tothe following reaction scheme:

The use of an excess of reactant in a chemical reaction makes itpossible to obtain better degrees of conversion and consequently betteryields of the desired product. However, the presence of residualelectrophilic reactant at the end of the reaction interferes with thepurification. A crosslinked polyimine according to the present inventionreacts with the excess electrophilic compound in the same way as asecondary amine in solution and a covalent bond is formed between thetwo entities. The excess electrophilic compound is thus destroyed andthe polyimine-electrophile entity can be removed from the reactionmedium by simple filtration, which simplifies the stages of isolationand purification of the desired product.

In addition, the process of the invention can be used for thepurification of acids by temporary attachment, according to thefollowing reaction scheme:

Any protic entity HX having a pKa of the HX/X⁻ pair which issubstantially lower (2 to 3 pKa units) than that of a secondary aminecan be bonded temporarily to the polyimine in order to make possible itspurification by filtration. A subsequent treatment with an excess ofbase will liberate the desired product. If the base chosen is volatile(for example NH₃), the product can be recovered in the pure state aftersimple evaporation, in the HX or NH₄X form, depending on the acidity ofHX. In this case also, the temporary fixing of the desired product tothe polyimine makes it possible to avoid tedious stages of extraction atdifferent pH values.

The present invention is described in more detail by the examples givenbelow, to which, however, it is not limited.

Example 1

Synthesis of polyimine

A mixture of ethylenediamine (1) (2 ml, 0.03 mol), oftris(2-aminoethyl)amine (3) (90 μl, 0.6 mmol), of1,4-bis(chloromethyl)benzene (2) (5.25 g, 0.03 mol) and of triethylamine(12.5 ml, 0.09 mol) in toluene was prepared and then this mixture wasbrought to reflux for approximately ten hours with stirring. Aftercooling, the polymer (4) formed was recovered by filtration, washedsuccessively with a 1M aqueous sodium hydroxide solution, with methanol,with ethyl acetate and with hexane, and then dried under vacuum. 4.4 gof dry polyimine were thus obtained, corresponding to a yield of 90%.

The reaction scheme corresponding to the achievement of the repeat unitsbetween the crosslinking nodes is shown below:

The polymer obtained was subjected to infrared analysis using a milledsample with KBr. The positions of the lines on the IR spectrum in cm⁻¹are as follows: 3370 (N—H), 2930, 2810, 1610, 1509, 1458, 1364, 1087(C—N), 822. The presence of a broad absorption band at 3370 cm⁻¹, due tothe stretching of the N—H bond, clearly shows that the product analyzedcomprises a high proportion of NH groups.

The degree of swelling (in ml/g) in various solvents is given below:

Hexane Dichloromethane THF Methanol DMF Water 3.0 4.8 4.2 5.6 4.4 5.0

These values show that the polyimine can be regarded as amphiphilic. Itcan consequently be used in a larger number of applications thancommercially available polystyrene polymers, such as for the trapping ofundesired compounds. This is because polystyrene polymers are completelyhydrophobic and they swell neither in water nor in methanol (<2 ml/g ofresin).

The reactivity of the NH groups was determined by bringing the polyimineinto contact with di(tert-butyl) dicarbonate (Boc₂O), which is arelatively hindered and weakly reactive electrophilic reactant. Thepolyimine was treated with an excess of Boc₂O. The reaction was carriedout in CDCl₃. The amount of Boc₂O which could be “absorbed” by thepolyimine is determined by subtraction of the amount remaining insolution from the initial amount, the measurements being carried out byproton NMR. This process gives a direct reading of the effective contentof amine in the polyimine. Thus, the calculation of the theoreticalcontent expected on the basis of the polymer mesh shows that thereshould be 12.3 mmol of amines per gram. The measurement of the effectivecontent for the trapping of Boc₂O gives a value of 10.9 mmol of NH pergram of resin, which means that almost 90% of the NH groups areaccessible, even for a relatively unreactive electrophile.

Example 2

Synthesis of Polyimine

A mixture of 1,7-heptanediamine (1.3 g, 10 mmol), oftris(2-aminoethyl)amine (30 pmol, 0.2 mmol), of1,4-bis(chloromethyl)benzene (1.75 g, 10 mmol) and ofdiisopropylethylamine (5.2 ml, 30 mmol) in DMF (5 ml) was prepared andthen this mixture was brought to 80° C. for 48 hours with stirring.After cooling, the polymer formed was recovered by filtration, washedsuccessively with a 2M aqueous sodium hydroxide solution, with distilledwater, with methanol, with ethyl acetate and with dichloromethane, andthen dried under vacuum for approximately ten hours. 2 g of drypolyimine were thus obtained, corresponding to a yield of 85%.

Theoretical content=8.7 mmol/g; Effective content for the trapping ofBoc₂O=7.5 mmol/g.

IR (milled sample with KBr, in cm⁻¹): 3325 (N—H stretch), 2930, 2830,1595, 1458, 1364.

Example 3

Synthesis of Polyimine

A mixture of 1,3-propanediamine (0.83 ml, 10 mmol), oftris(2-aminoethyl)amine (30 μmol, 0.2 mmol), of1,4-bis(chloromethyl)benzene (1.75 g, 10 mmol) and ofdiisopropylethylamine (5.2 ml, 30 mmol) in DMF (5 ml) was prepared andthen this mixture was brought to 80° C. for 48 hours with stirring.After cooling, the polymer formed was recovered by filtration, washedsuccessively with a 2M aqueous sodium hydroxide solution, with distilledwater, with methanol, with ethyl acetate and with dichloromethane, andthen dried under vacuum for approximately ten hours. 1.6 g of drypolyimine were thus obtained, corresponding to a yield of 91%.

Theoretical content=12.3 mmol/g; Effective content for the trapping ofBoc₂O=11.5 mmol/g.

IR (milled sample with KBr, in cm⁻¹): 3360 (N—H stretch), 2930, 2830,1610, 1458, 1364.

Example 4

Trapping of Sulfuric Acid in the Aqueous Phase

A crosslinked polyimine obtained according to the procedure of example 1(64 mg, 0.64 mmol, ≈3 eq.) was added to a solution of sulfuric acid(12.0 mg, 0.122 mmol) in distilled water (0.5 ml, C=0.24, M≈0.5 N,pH=0.3). The resin swelled well and, after one hour, the pH of thesolution was in the vicinity of 6. The concentration of protons is thus10⁻⁶N, which means that the trapping of the H⁺ ions is quantitative(>99.9%).

Example 5

Trapping of HCl in the Aqueous Phase

crosslinked polyimine prepared according to example 1 (52 mg, 0.52 mmol,≈3 eq.) was added to a solution of hydrochloric acid (18 mg, 35%, 0.173mmol) in distilled water (0.5 ml, C=0.345M/N, pH =0.46) . The resinswelled well and, after one hour, the pH of the solution was in thevicinity of 6. The concentration of protons is thus 10⁻⁶N, which meansthat, here again, the trapping of the H⁺ ions is quantitative (>99.9%).

Example 6

Trapping of Para-toluenesulfonic Acid (CH₂Cl₂)

A mixture of p-toluenesulfonic acid monohydrate (TsOH) (7.5 mg, 39.4μmol) and of pentamethylbenzene (6.6 mg, 44.5 μmol, internal standard)in solution in dichloromethane (300 μl) was treated with 3 equivalentsof polyimine prepared according to example 1 (12 mg, 120 μmol). Afterfiltering and evaporating, it was observed, by NMR, that theTsOH/pentamethylbenzene ratio was 0.02. Thus, only 0.89 μmol of TsOHremains in the medium, i.e. only 2% of the initial amount.

Example 7

Trapping of Para-toluenesulfonic Acid (Methanol)

A mixture of TsOH monohydrate (8.4 mg, 44.2 μmol) and ofpentamethylbenzene (6.8 mg, 45.85 μmol, internal standard) in solutionin CD₃OD (300 μl) was treated with 3 equivalents of polyimine preparedaccording to example 1 (13.5 mg, 14 μmol). After filtering, it wasobserved, by NMR, that the TsOH/pentamethylbenzene ratio was 0.01. Thus,only 0.46 μmol of TsOH remains in the medium, i.e. only 1% of theinitial amount.

Example 8

Trapping of an Electrophilic Compound

Dibenzylamine (96 μl, 0.5 mmol), in solution in CDCl₃ (2 ml) comprisinga small amount of dimethylaminopyridine (DMAP) as catalyst (6 mg, 0.05mmol), was treated with an excess of Boc₂O (218 mg, 1 mmol) to producethe carbamate (PhCH₂)₂N—Boc. After 1 hour, a crosslinked polyimineprepared according to example 1 (140 mg, 1.5 mmol of NH, 3 equivalentswith respect to the excess of the electrophilic compound Boc₂O) wasadded. The reaction mixture was stirred for approximately ten hours atambient temperature and then the polyimine was removed by filtrationthrough cotton wool. The ¹H NMR spectrum shows that the excess Boc₂O hasindeed been removed by this postreaction treatment.

1. A crosslinked polyimine comprising linear segments composed of—HN—R¹—NH—R²—Ar—R³— units in which R¹, R² and R³ are identical ordifferent alkylene or alkenylene groups and Ar represents an aromaticgroup.
 2. The polyimine as claimed in claim 1, wherein the alkylene oralkenylene groups have from 1 to 10 carbon atoms.
 3. The polyimine asclaimed in claim 1, wherein Ar is a φ or φ-φ group in which φ representsa phenyl optionally carrying one or more substituents.
 4. The polyimineas claimed in claim 1, wherein the substituents of the phenyl group arechosen from alkyl, aryl, alkyloxy, alkoxycarbonyl, halogen or NO₂groups.
 5. The polyimine as claimed in claim 1, wherein the crosslinkingnodes are of the N(R⁴NH—R²—Ar—R₃—)₃ or C(R⁴NH—R²—Ar —R³)₄ _(—) _(n)(R⁴NH₂)_(n) or type in which R⁴ represents an alkylene group and n is 0or
 1. 6. The polyimine as claimed in claim 5, wherein the alkylene grouphas from 1 to 10 carbon atoms.
 7. The polyimine as claimed in claim 1,wherein it has a content of NH groups of the order of 11 mmol/g.
 8. Aprocess for the removal of organic acid or inorganic acids present in ahydrophobic reaction medium or in a hydrophilic reaction medium, whichcomprises bringing a crosslinked polyimine according to claim 1 incontact with said acid compounds and then separating a modifiedpolyimine product.
 9. A process for the removal of electrophiliccompounds present in a hydrophobic reaction medium or in a hydrophilicreaction medium, which comprises bringing a crosslinked polyimineaccording to claim 1 in contact with said electrophilic and thenseparating a modified polyimine product.
 10. The process of claim 8,wherein the process further comprises treating the modified polyimineproduct with a base.
 11. A process for immobilizing acidic orelectrophilic compounds present in a solvent, wherein the processcomprises bringing a crosslinked polyimine, into contact with saidcompounds, and in separating, by filtration, the modified polyimineobtained, wherein the crosslinked polyimine is a polyimine according toclaim
 1. 12. The process as claimed in claim 1, wherein the contactingoperation is carried out at ambient temperature.
 13. The process asclaimed in claim 1, wherein the duration of the contact is between 1hour and approximately 10 hours.